H2A is a nucleosome core subunit involved in organizing DNA into a chromatin structure that is often inaccessible to regulatory enzymes. Replacement of H2A by its variant H2A.Z renders chromatin accessible at enhancers and promoters. However, it remains unclear how H2A.Z functions so differently from canonical H2A. Here we report the genome-wide identification of proteins that directly interact with H2A and H2A.Z in vivo using a novel strategy, bPPI-seq. We show that bPPI-seq is a sensitive and robust technique to identify protein-protein interactions in vivo. Our data indicate that H2A.Z-interacting proteins and H2A-interacting proteins participate in distinct biological processes. In contrast to H2A-interacting proteins, the H2A.Z-interacting proteins are involved in transcriptional regulation. We found that the transcription factor Osr1 interacts with H2A.Z both in vitro and in vivo. It also mediates H2A.Z incorporation to a large number of target sites and regulates gene expression. Our data indicate that bPPI-seq can be widely applied to identify genome-wide interacting proteins under physiological conditions.

中文翻译：

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通过bPPI-seq对组蛋白H2A和组蛋白变异H2A.Z相互作用蛋白进行全基因组鉴定。

H2A是一个核小体核心亚基，参与将DNA组织成通常无法通过调节酶进入的染色质结构。用其变体H2A.Z替代H2A，使染色质可进入增强子和启动子。但是，目前尚不清楚H2A.Z与标准H2A有何不同。在这里，我们报告使用新策略bPPI-seq在体内直接与H2A和H2A.Z相互作用的蛋白质的全基因组鉴定。我们表明，bPPI-seq是一种敏感而强大的技术，可以识别体内的蛋白质-蛋白质相互作用。我们的数据表明，H2A.Z相互作用蛋白和H2A相互作用蛋白参与不同的生物学过程。与H2A相互作用蛋白相反，H2A.Z相互作用蛋白参与转录调控。我们发现转录因子Osr1在体外和体内均与H2A.Z相互作用。它还介导H2A.Z掺入大量靶位并调节基因表达。我们的数据表明，bPPI-seq可以广泛应用于在生理条件下鉴定全基因组相互作用的蛋白质。